The broad objective of research proposed herein is to elucidate the physical-biochemical strategy of genetic adaptation in microorganism populations and to determine the degree to which these adaptive strategies can be predicted and directed. The research approach is based upon the assumption that analysis of Darwinian experiments on microorganism populations subjected to appropriate chemostat environments can lead to an elucidation of the basic physical-biochemical mechanisms through which organisms adapt to given environmental stresses; that such knowledge should contribute to the construction of a physical-biochemical interpretation of some of the central dogma of population genetic theory and lead toward an elucidation of genetic adaptation as a natural consequence of physical- biochemical law, thus integrating the disciplines of population genetics and evolution with those of biochemistry and molecular genetics; and finally, that such information can provide a major contribution to the development of theory, methodology and technology required to effectively direct the process of genetic adaptation of microorganism populations for medical and other applications. The specific objectives of research proposed herein are: to continue an analysis of the physical-biochemical strategy of genetic adaptation of the external hydrolytic enzymes of S. cerevisiae; and to further pursue our study of the basis of diploidy as an adaptive strategy.